Liquid formulas, in particular for enteral nutrition, contain protein in a concentration ranging from 2 to 6%. Most of these type products have 3 to 4% (30-40 g/l) of protein, and more rarely contain protein concentrations of >50 g/l to 80 g/l. If the existing products are reviewed with respect to their protein source, it appears that most formulas were based on casein (Ca—, Na— or K-caseinate), and more recently also on milk protein concentrate (MPC).
At present, liquid shelf stable formulas based on intact whey protein are practically non-existant. This is related to the pronounced heat lability of whey protein in sterilizing heat treatments, a problem not experienced when casein is used as a protein source.
In consideration of the high nutritional protein quality (balanced aminogramme) of whey protein, the use of this protein source in enteral nutrition formulas appears very desirable. Due to heat induced gelling or sedimentation, however, it has not been possible so far to incorporate into suhc formulas markedly higher concentrations of whey protein than e.g. that present in commercial milk protein concentrates (milk protein concentrate whey proteins constitute about 20% of the total protein). Sterilizing heat treatments such as those required for bacteriological safety and non-refrigerated storage lead to denaturation of the protein, followed by aggregation, sediment formation or gelling of the protein in the formula.
A known solution to this stability problem is the partial hydrolysis of whey protein by proteases, prior to the introduction of the material into a composition that is subjected to sterilizing heat treatments.
An example of a commercial enteral formula containing 40 g/l of partially hydrolysed whey protein is known as PEPTAMEN®. In this product, the protein has been partially hydrolysed by trypsin and thereby rendered stable to sterilizing heat treatment. It is also possible to combine whey protein hydrolysates with casein hydrolysates or cascinates to compose the protein basis of a formula. An example of such an approach is disclosed in U.S. Pat. No. 5,821,217 (an enteral formula containing protein hydrolysates) or in U.S. Pat. No. 5,549,905 (a pediatric patients formula containing 12% of the calories in form of hydrolysed whey protein).
Although the use of partially hydrolysed (whey) protein is a possible approach, an inherent disadvantage of this solution is the bitter taste resulting from the incorporation of partially hydrolysed protein into such formulas. While bitter taste is not a significant problem in a tube feeding mode, it becomes a serious problem in a formula intended for oral consumption.
In order to produce a bland tasting whey protein based enteral formulas with long non-refrigerated shelf life, approaches other than hydrolysis must be found to stabilize the protein or else the formula will not be palatable.
Two recent developments seem to go in this direction, but they do not achieve the goal of sterility and long shelf life which exploit the known acid stability of whey protein. EP 0 486 425 teaches the production of a whey protein based formula (at least 60% whey protein) which as a pH between 3.5 and 3.9. The low pH of the formula was obtained by the addition of citric and phosphoric acid. The formula received a pasteurizing heat treatment: at 95.6° C. for 4.3 s. In WO 99/56563, a low pH enteral formula is described in which highly methoxylated pectin (0.6-1.25%) is used as a protein stabilizer. One particular variant of this formula contains intact whey protein as a protein source; the final pH of the formula is 4.0-4.35 and the heat treatment applied to the formula is 102-104° C. for 18 s.
Both these disclosures are first steps towards a successful incorporation of intact whey protein into liquid enteral nutrition formulas, but they both have the decisive shortcoming of being unable to deliver shelf-stable products. This is evident if one looks at the heat treatments being used. Both heat treatments provide sufficient killing of vegetative non-spore forming bacteria but cannot inactivate spore formers to any sufficient extent. In order to inactivate e.g. spores of B.cereus, heat treatments well above 105° C. are required. B.cereus has a known D-value in the range of 40-100 s at an acid pH. The heat treatment given e.g. in WO 99/56563 (102-104° C./18 s) will provide less than one log of inactivation. With a treatment at 130° C., and D130=0.1 s, close to 10 logs of inactivation per second of holding time are achieved for the same organism. For thermophilic spore formers such as B. steatiothermophilsu, B. coagulans or B. circulans, D-values are >100 s at an acid pH. It is therefore clear that heat treatments such as used in both documents cannot lead to commercial sterility or to a satisfactory non-refrigerated shelf life.
A further disadvantage of the processes described in these two documents is doubtless the strongly sour taste of the products, which also limits the flavoring possibilities and by this also narrows acceptance by the consumer.
A third shortcoming of the approach described in these two documents is the fact that with a pH of the formula in a range of 3 to 4.6, no casein can be included in the formula, as under these conditions, casein is precipitated or forms a gel. This excludes the production of liquid formulas with combinations of whey protein and casein.
According to the teachings of the prior art so far, there is no solution to the problem of producing a commercially sterile, shelf-stable liquid formula, with a neutral pH and based exclusively or to its major part, on intact (unhydrolysed) whey protein. The present invention now provides one solution to this problem.